Colleges
Hugh Watkins
FRS FMedSci
Radcliffe Professor of Medicine
- British Heart Foundation Professor of Cardiovascular Medicine
- Honorary Consultant in Cardiology and General Medicine
- Principal Investigator of CureHeart
- Director of the BHF Centre for Research Excellence
Molecular Genetics and Molecular Biology of the Heart Muscle Disease/Molecular Genetics of Complex Cardiovascular Phenotypes
My interest is in using molecular genetic analysis of cardiovascular disease as a tool to define disease mechanisms and therapeutic targets. I have had a longstanding focus on inherited heart muscle diseases, in particular hypertrophic cardiomyopathy, which is a relatively common Mendelian condition which puts affected individuals at risk of sudden cardiac death. My group's work, using molecular biological, model organism and clinical research approaches, has lead to the idea that energy compromise is a key disease mechanism; clinical trials are underway to test new medical therapies based on this finding. Our work on genetic causes of ‘sudden cardiac death’ syndromes has been translated into clinical practice through the Oxford BRC, leading to an NHS commissioned national DNA diagnostic service. This area of my work is integrally linked with the groups of Dr. Charles Redwood and Dr. Houman Ashrafian as we have worked closely together for many years.
I also lead a research group investigating susceptibility genes for coronary artery disease, now the main cause of premature mortality worldwide. With colleagues in Oxford (Profs Farrall and Collins) and in Europe (Prof Hamsten, Karolinska) I established the Procardis study to assemble the large scale clinical collections needed to tackle this challenge; I have since chaired a large international collaboration in this area (the C4D Consortium). Recent findings include evidence that lipoprotein Lp(a) levels are causally related to coronary disease risk and identification of multiple novel common susceptibility variants for coronary artery disease risk. This work is now entering an exciting phase where we can use functional genomic tools to understand new biology, thus drawing on some of the approaches we have developed in our Mendelian genetic work.
Key publications
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Association analyses based on false discovery rate implicate new loci for coronary artery disease
Journal article
Nelson CP. et al, (2017), Nature Genetics, 49, 1385 - 1391
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Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function
Journal article
Yavari A. et al, (2016), Cell Metabolism, 23, 821 - 836
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Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples
Journal article
Walsh R. et al, (2017), Genetics in Medicine, 19, 192 - 203
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A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease
Journal article
(2015), Nature Genetics, 47, 1121 - 1130
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Combination of Whole Genome Sequencing, Linkage, and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy With Features of Left Ventricular Noncompaction
Journal article
Hastings R. et al, (2016), Circulation: Cardiovascular Genetics, 9, 426 - 435
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Fumarate Is Cardioprotective via Activation of the Nrf2 Antioxidant Pathway
Journal article
Ashrafian H. et al, (2012), Cell Metabolism, 15, 361 - 371
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Metabolic Modulator Perhexiline Corrects Energy Deficiency and Improves Exercise Capacity in Symptomatic Hypertrophic Cardiomyopathy
Journal article
Abozguia K. et al, (2010), Circulation, 122, 1562 - 1569
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Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease
Journal article
Clarke R. et al, (2009), New England Journal of Medicine, 361, 2518 - 2528
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
Journal article
Speliotes EK. et al, (2010), NATURE GENETICS, 42, 937 - U53
Recent publications
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Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.
Journal article
Coats CJ. et al, (2024), European heart journal, 45, 4464 - 4478
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Multiparametric CMR Evaluation of Myocardial Perfusion, Oxygenation, and Energetics in Hypertrophic Cardiomyopathy Following Cardiac Myosin Inhibitor Therapy.
Journal article
Finnigan LEM. et al, (2024), European heart journal. Cardiovascular Imaging
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Protein Biomarkers of Adverse Clinical Features and Events in Sarcomeric Hypertrophic Cardiomyopathy.
Journal article
Tahir UA. et al, (2024), Circulation. Heart failure
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AnALPK3truncation variant causing autosomal dominant hypertrophic cardiomyopathy is partially rescued by mavacamten
Preprint
Leinhos L. et al, (2024)
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Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.
Journal article
Huffman JE. et al, (2024), Blood